Clinical Efficacy and Mechanism of Erzhi Tiangui Prescription in Treatment of Patients with Repeated Implantation Failure of Kidney Deficiency Syndrome Based on sPD-1 and Th17/Treg Cytokines / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and possible mechanism of Erzhi Tiangui prescription on repeated implantation failure （RIF） of kidney deficiency syndrome. MethodSeventy patients with RIF of kidney deficiency syndrome who underwent natural cycle frozen-thawed embryo transfer （FET） in the Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were enrolled and randomly divided into a treatment group （35 cases） and a control group （35 cases）. Patients in the treatment group took oral Erzhi Tiangui prescription from the third day of each menstrual cycle two months before the FET cycle and continued to take it until the day of transplantation from the third day of the menstrual cycle in the month of transplantation. Those in the control group did not accept traditional Chinese medicine （TCM）. In addition，10 patients who successfully achieved clinical pregnancy after the first natural cycle FET were screened from the reproductive medical record bank of this hospital and assigned to the normal group. Peripheral blood samples of patients in the three groups on the day of embryo transfer were collected from the specimen bank of the Reproductive and Genetic Center. Serum soluble programmed death molecule-1 （sPD-1），soluble programmed death molecule-ligand 1 （sPD-L1），transforming growth factor-β （TGF-β），interleukin-17 （IL-17）， and interleukin-10 （IL-10） levels were measured by enzyme-linked immunosorbent assay （ELISA）. The changes in kidney deficiency syndrome scores， the final biochemical pregnancy rates， clinical pregnancy rates， and embryo implantation rates of the treatment group and the control group before and after treatment were observed. ResultCompared with the normal group，the model group showed increased serum levels of sPD-1 and IL-17（r=0.347，P<0.05），decreased levels of IL-10 and TGF-β （P<0.01），and non-significant change in sPD-L1 level. Serum sPD-1 was positively correlated with IL-17 （P<0.05） and negatively correlated with IL-10（r=-0.521，P<0.01） and TGF-β（r=-0.457，P<0.01） in RIF patients with kidney deficiency syndrome. After TCM treatment，compared with the control group， the treatment group showed improved TCM syndrome score （P<0.05） and increased clinical pregnancy rate and embryo transfer rate（P<0.05），but there was no statistically significant difference in the biochemical pregnancy rate between the two groups. ConclusionAbnormal expression of sPD-1 in patients with RIF of kidney deficiency syndrome breaks the balance of T helper 17 （Th17）/regulatory T cell （Treg），which is not conducive to embryo implantation and pregnancy maintenance. Erzhi Tiangui prescription，a TCM for tonifying the kidney，can significantly improve the symptoms of kidney deficiency in patients with RIF of kidney deficiency syndrome，reduce the concentrations of sPD-1 and IL-17 in the peripheral serum，increase the levels of TGF-β and IL-10，regulate the peripheral Th17/Treg immune balance，and increase the implantation rate and clinical pregnancy rate，which has a high clinical value.

Research progress on clinical application of soluble PD-1 in anti-tumor therapy / 中国肿瘤生物治疗杂志

@#[摘 要] 程序性死亡蛋白-1（programmed death protein 1，PD-1）是表达在T细胞表面的一种重要的免疫抑制穿膜蛋白，在限制慢性炎症、感染或肿瘤中T细胞的活性方面起重要作用。可溶性PD-1（soluble PD-1，sPD-1）是由PD-1缺失3号外显子的转录剪接体转录翻译而来，无法形成穿膜区，但其具有胞外结构域，具有与配体PD-L1/PD-L2结合的能力，能激活T细胞并促进DC成熟，而发挥抗肿瘤作用。随着免疫疗法及免疫检查点阻断治疗的出现并逐渐成为肿瘤治疗的新兴手段，关于PD-1及其抗体的基础及临床转化研究也成为肿瘤研究的热点之一。不同形式的PD-1被发现，意味着PD-1可能在机体中发挥着更加复杂及多面的功能，因此对于sPD-1的研究也逐渐展开及深入。本文就sPD-1作为肿瘤诊断、疗效预测及预后评估的潜在标志物及联合抗肿瘤免疫治疗中的临床应用研究进展作一综述，以期了解sPD-1在抗肿瘤治疗中的重要作用，为肿瘤免疫治疗提供新思路、新方法和新策略。

Inhibitory effect on pulmonary metastasis of melanoma in mice by soluble PD-1 and its combina-tion with HspT0-B16 antigen peptides / 中华皮肤科杂志

Objective To investigate the blockade effects of soluble PD-1 (sPD-1) expressed in vivo on B7-H1/PD-1 signal transduction,and inhibitory effect in pulmonary metastasis of melanoma with combi- nation of Hsp70-B16 antigen peptides in mice.Methods The pulmonary metastasis model of melanoma was established in mice.Immunohistochemical staining and flow cytometry were utilized to detect the expres- sion of PD-1 and B7-H1 respectively in pulmonary metastasis loci.Four days after the inoculation of tumor cells,forty murine models of pulmonary metastasis were randomly divided to be immunized with normal sodium (group A),empty vector pcDNA3.1 (group B),PDlA plasmid (group C) respectively via tail vein injection,subcutaneous injection of Hsp70-B16 antigen peptides (group D) or with the combination of intra- venous PDlA plasmid and subcutaneous Hsp70-B 16 antigen peptides (group E).The local infiltration with lymphocytes in pulmonary metastasis loci was observed and a series of immunological parameters were assessed 17 days after the inoculation of tumor cells.Results The melanoma pulmonary metastasis model was successfully established.There were a lot of PD-1 positive cells in these loci,and B7-H1 molecule was massively expressed on the surface of B16 cells in metastasis loci.The pulmonary metastasis was inhibited in the mice of group E,and the inhibition rate was 95%,higher than that in other groups (53%,76%,9% in group C,D,B,respectively).The quantity of CD8~+ T cells in pulmonary metastasis loci,cytotoxicity of spleen lymphocytes to tumor cells,and serum concentration of IL-2 and IFN-?were all significantly elevated in the mice of group E as compared with those of other groups (all P